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[Image diagnosis of adrenal disorders--I. CT images of control subjects and image diagnosis of primary aldosteronism].

The shape and size of the adrenals in control subjects without adrenal disorders were studied by computed tomography (CT), and a comparative assessment of diagnostic values of ultrasonography (US) by electronic linear scanner, CT, and adrenal scintigraphy was made on 9 patients with primary aldosteronism. Adrenal imaging by scintigraphy was performed on the 5th and 6th day, or further on the 7th day after the injection of 1 mCi of Adosterol. CT findings of the adrenals in control subjects: Eighty-two % of 100 control right adrenals, and 89% of 100 control left adrenals were detected by CT. Seventy-seven % of the right adrenals were in linear-shape, and the others were in V-shape. The shape of the left adrenals could be classified into triangular-shape (54%), Y-shape (28%) and V-shape (18%). The mean width and thickness of the right adrenals were 28.6 +/- 7.5 mm (M +/- SD) and 3.8 +/- 1.4 mm, respectively. Those of the left ones were 19.4 +/- 5.5 mm and 5.3 +/- 1.8 mm. Image diagnosis of primary aldosteronism: In 2 out of 3 patients examined by US, aldosteronomas were detected. In these 2 patients, one had 2 adenomas 2.8 X 1.7 X 1.2 cm and 1.0 X 1.0 X 2.0 cm in size, and the other had one adenoma 0.8 X 1.0 X 2.0 cm in size. On adrenal scintiscanning under dexamethasone pretreatment (DP), the isotope uptake of aldosteronoma was still seen with the disappearance of the contralateral adrenal in 7 out of 9 cases. In these 7 cases, the laterality of the tumor was confirmed. In one of the remaining 2 cases, the bilateral adrenal images were obtained regardless of DP. In the other case, of which aldosteronoma was the smallest (0.6 X 0.6 X 0.8 cm), the image of the affected adrenal with adenoma as well as the contralateral adrenal disappeared under DP. CT delineated all aldosteronomas in 8 cases examined including 2 cases in which adrenal scintiscanning failed to elucidate the localization of aldosteronoma. These results indicated that the combination of these 3 new image diagnostic methods was available for the detection of aldosteronomas of various sizes.

Adenoma↗

CT of primary hyperaldosteronism (Conn's syndrome): the value of measuring the adrenal gland.

OBJECTIVE: The objectives of our study of patients with primary hyperaldosteronism (Conn's syndrome) were to determine whether the adrenal glands are larger in patients with bilateral adrenal hyperplasia than in those with aldosterone-producing adenomas or in healthy control subjects; and whether a CT criterion based on adrenal gland size can be developed to positively diagnose bilateral adrenal hyperplasia. MATERIALS AND METHODS: A retrospective study of CT scans of 28 patients with primary hyperaldosteronism was performed. The means of two observers' measurements of adrenal gland size were recorded and compared with published normal values. In addition, a radiologist experienced in adrenal imaging and unaware of the cause of the primary hyperaldosteronism diagnosed either bilateral adrenal hyperplasia or aldosterone-producing adenoma by visual inspection. RESULTS: The adrenal glands in patients with bilateral adrenal hyperplasia were significantly (p < 0.05) larger than those in patients with aldosterone-producing adenoma or in healthy control subjects. A sensitivity of 100% was achieved when a mean limb width of greater than 3 mm was used to diagnose bilateral adrenal hyperplasia, and a specificity of 100% was achieved when the mean limb width was 5 mm or greater. Receiver operating characteristic curve analysis showed that the overall performance of the radiologist and the mean adrenal limb width in detecting bilateral adrenal hyperplasia were equivalent. CONCLUSION: In patients with primary hyperaldosteronism, adrenal limb measurements on CT can aid in differentiating bilateral adrenal hyperplasia from aldosterone-producing adenoma because the adrenal glands in bilateral adrenal hyperplasia are larger.

Adrenal Glands↗

Role of multidetector row computed tomography in the assessment of adrenal gland injuries.

OBJECTIVE: To determine the prevalence of adrenal injuries in a group of patients submitted to multidetector row CT evaluation after blunt trauma and to assess the impact of CT findings on clinical management decisions. MATERIALS AND METHOD: During a 4-year period, 2026 emergency CT examinations were performed in the setting of major blunt trauma. A total of 82 patients were retrospectively identified as having adrenal gland traumatic lesions. At multidetector row CT the following findings were considered specific of adrenal injury: round or oval hematoma expanding the adrenal gland, irregular hemorrhage obliterating the gland, uniform adrenal gland swelling, active extravasation of contrast material from the adrenal vessels and adrenal gland rupture. Associated CT findings were: stranding of the periadrenal fat, diffuse hemorrhage in the adjacent retroperitoneum and compression of the adrenal gland by adjacent traumatic lesions. RESULTS: We identified 82 patients (46 males and 36 females, age ranging from 15 to 86 years) with adrenal injuries. The right adrenal gland was injured in 60/82 patients, while the left adrenal gland was injured in 21 cases; in 1 patient bilateral adrenal gland traumatic lesions occurred. In 76 patients with non-isolated adrenal injuries concomitant injuries to the liver (49 cases), ipsilateral kidney (18 cases) and spleen (9 cases) were observed. Round or oval hematoma expanding the adrenal gland (61 cases), irregular hemorrhage obliterating the gland (14 cases), stranding of the periadrenal fat (9 cases) and diffuse hemorrhage in the adjacent retroperitoneum (8 cases) were the more frequent findings detected at CT. Six patients underwent surgical intervention for the presence of major injuries to the spleen (three cases), to the liver (one), to the right kidney (one), to the left kidney (one). Seventy-six patients were conservatively treated. CONCLUSION: Blunt adrenal injuries typically present as part of a multiorgan trauma. Familiarity with characteristic CT findings of adrenal trauma is essential for the radiologist to avoid misdiagnosis.

Abdominal Injuries↗

Metastatic tumours of the adrenal glands: a 30-year experience in a teaching hospital.

OBJECTIVE: Adrenal metastases are frequently encountered during autopsy but uncommonly present clinically. The aim of this study was to evaluate the clinical and pathological impact of adrenal metastases in a large series of patients. PATIENTS: Four hundred and sixty-four patients (288 men, 176 women) with metastatic disease in the adrenal glands over a 30-year period were included in the study. MEASUREMENTS: The clinical records and pathological features were reviewed. RESULTS: The frequencies of adrenal metastases at autopsies, adrenalectomies and fine-needle aspiration biopsies were 3.1%, 7.5% and 33%, respectively. The lesions were often seen in elderly patients (mean age, 62, SD = 13 years). Many of the metastatic lesions in the adrenal gland occurred shortly after the detection of a primary tumour (mean latent period = 7 months). Four per cent of the adrenal lesions (n = 20) were symptomatic. The symptomatic adrenal lesions, as compared with asymptomatic ones, were bigger and seen in younger patients. Five patients presented with adrenal insufficiency (Addison's disease) and one had massive peritoneal haemorrhage because of metastatic carcinoma. Ninety per cent (n = 421) of the metastatic adrenal tumours were carcinomas and 56% of these were adenocarcinoma. Lung was the most common primary tumour site (35%), followed by the stomach (14%), the oesophagus (12%) and the liver/bile ducts (10%). The adrenal metastases were bilateral in approximately half of the patients (49%, n = 229). The mean diameter of the adrenal metastases was 2 cm (SD = 1.9 cm). The mean weight of the right adrenal gland harbouring the metastasis was 19 g, while that of the left 20 g. The median survival of the 20 patients with symptomatic adrenal lesions was 3 months (range, 0-75 months) after the detection of adrenal metastases. Patients with surgically removed adrenal metastases had slightly better survival rates than those without surgical resection. CONCLUSIONS: A variety of tumours may give rise to adrenal metastases. They are often asymptomatic and detected as part of multiorgan metastases. Symptomatic cases, albeit rare, may occur. Long-term survival may be achieved in selected patients in whom an aggressive surgical approach may be adopted.

Adenocarcinoma↗

The diagnostic role of radionuclide imaging in evaluation of patients with nonhypersecreting adrenal masses.

UNLABELLED: The aim of this study was to evaluate the role of radionuclide imaging in the characterization of nonhypersecreting adrenal masses. METHODS: A total of 54 patients (19 men, 35 women; mean age, 50 +/- 16 y) with nonhypersecreting unilateral adrenal tumors that had been originally detected on CT or MRI underwent adrenal scintigraphy using different radiotracers. None of the patients showed specific symptoms of adrenal hypersecretion. Screening tests for excess cortical and medullary products showed normal adrenal hormone levels. Radionuclide studies (n = 73) included (131)I-norcholesterol (n = 24), (131)I-metaiodobenzylguanidine (MIBG) (n = 23), and (18)F-FDG PET (n = 26) scans. RESULTS: Histology after surgery (n = 31) or adrenal biopsy (n = 23) was obtained. Adrenal lesions were represented by 19 adenomas, 4 cysts, 1 myelolipoma, 1 neurinoma, 2 ganglioneuromas, 5 pheochromocytomas, 4 pseudotumors, 6 carcinomas, 2 sarcomas, and 10 metastases (size range, 1.5- to 5-cm diameter; mean, 4.9 +/- 3.1 cm). For norcholesterol imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 71%, and 92%, respectively; the positive predictive value (PPV) of the norcholesterol scan to characterize an adrenal mass as an adenoma was 89%, whereas the corresponding negative predictive value (NPV) to rule out this type of tumor was 100%. For MIBG imaging, diagnostic sensitivity, specificity, and accuracy were 100%, 94%, and 96%, respectively; the PPV of the MIBG scan to characterize an adrenal mass as a medullary chromaffin tissue tumor was 83%, whereas the corresponding NPV to rule out this type of tumor was 100%. For FDG PET, diagnostic sensitivity, specificity, and accuracy were 100%, 100%, and 100%, respectively; the PPV of FDG PET to characterize an adrenal mass as a malignant tumor was 100%, whereas the corresponding NPV to rule it out was 100%. Furthermore, in 7 patients with malignant adrenal tumors, FDG whole-body scanning revealed extra-adrenal tumor sites (n = 29), allowing an accurate diagnosis of the disease's stage using a single-imaging technique. CONCLUSION: In patients with nonhypersecreting adrenal masses, radionuclide adrenal imaging, using specific radiopharmaceuticals such as norcholesterol, MIBG, and FDG, may provide significant functional information for tissue characterization. Norcholesterol and MIBG scans are able to detect benign tumors such as adenoma and pheochromocytoma, respectively. Conversely, FDG PET allows for recognition of malignant adrenal lesions. Therefore, adrenal scintigraphy is recommended for tumor diagnosis and, hence, for appropriate treatment planning, particularly when CT or MRI findings are inconclusive for lesion characterization.

19-Iodocholesterol↗

Ths significance of metastases to the adrenal glands in adenocarcinoma of the colon and rectum.

A study to determine the frequency of metastases to the adrenal glands following carcinoma of the colon and rectum was undertaken. Patients with, or without, adrenal spread were compared regarding age, sex, race and survival time. The over-all metastatic pattern was analyzed to determine its usefulness for predicting the presence of metastases to the adrenal glands. Autopsy reports and clinical records of patients with adrenal spread were reviewed regarding the extent of tumor involvement in the glands and possible adrenal insufficiency. Of 457 patients with adenocarcinoma of the colon and rectum who underwent autopsy, 63 or 14% had metastasis to the adrenal glands. Of these, 29 had bilateral involvement. Patients with bilateral metastases had a lower median age than did those without adrenal spread. No correlation was found between adrenal metastatic status and sex or race. Although survival time was found to be shorter for patients with bilateral metastases of the adrenal glands, adrenal insufficiency did not seem to be the reason for this shorter survival time. In retrospect, however, the presence of adrenal insufficiency could not be ruled out in several of these patients. Eight sites were studied with regard to whether or not metastatic involvement in a specific site might indicate a higher risk for simultaneous metastases to the adrenal glands. It was found for all sites that, when involved, there was a higher frequency of metastases to the adrenals than if free of tumor. Metastases especially above the diaphragm indicated a considerable risk for adrenal involvement. Different sites were combined in groups and studied in the same way. It was found that the more sites involved, the higher the relative chance of metastases to the adrenals. It was suggested that the results presented may be useful in predicting the relative chance of adrenal metastases in patients with advanced carcinoma of the colon and rectum.

Adenocarcinoma↗

Long-term outcome of the fetal adrenal gland transplantation in rats.

Three experimental groups have been constructed to evaluate the long-term outcome of fetal adrenal transplantation in rats. In Group 1 (n = 10), rats underwent bilateral adrenalectomy. In Group 2 (n = 10), rats underwent a sham procedure which included flank incision and arterial canulization. In Group 3 (n = 20), a left adrenalectomy was performed followed immediately by transplantation of a fetal adrenal graft into the greater omentum and marked with a prolene suture (Stage 1). One year later, the right adrenal gland of the recipient was removed followed by a determination of the fetal adrenal graft function (Stage 2). Graft function was evaluated by measuring ACTH and corticosterone levels; and a histologic examination of the transplanted fetal adrenal gland was obtained at autopsy. In Group 1, all the rats died within first 8 hours, following bilateral adrenalectomy. In Group 2, and Group 3, all rats survived after Stage 1 operation. During the Stage 2 operation, it was observed that three rats (15%) had neither fetal adrenal transplant nor prolene suture, seven rats (35%) had a well vascularized and developed fetal adrenal graft and a prolene suture. There was no visible fetal adrenal graft but the prolene suture was present in the remaining rats (50%) in Group 3. After removal of the right adrenal gland (6 and 12 hours later), the mean plasma level of ACTH increased with a decline in mean serum corticosterone level in Group 3 compared to the sham-operated animals (p < 0.001). In spite of visible, and viable transplants, all rats died within 48 hours following Stage 2 operation. The mean weight of the fetal adrenal transplant showed a sixteen-fold increase compared to the initial weight (p < 0.001) and histologic examination showed all 3 zones of adrenal cortex, but there were no medullary cells noted. Although the transplanted fetal adrenal grafts survived, their hormonal function was not enough to maintain host viability. Based on these results it is concluded that, insufficiency of the transplanted fetal adrenal gland may be secondary to either graft rejection or suppression of the transplanted tissue by the functional recipient adrenal despite the fetal adrenal transplant survival.

Adrenal Cortex Function Tests↗

Magnetic resonance imaging of the adrenal gland.

The authors review their experience with magnetic resonance imaging (MRI) of the adrenal gland and discuss the appearance of adrenal diseases where MRI is clinically useful. A basic description of some of the newer pulse sequences is provided. Fat-suppressed MRI is advantageous because of reduction of cardiac and respiratory motion induced artifacts, accentuation of small differences in tissue contrast, and elimination of chemical shift artifacts. These advantages far outweigh the disadvantages of inhomogeneity of fat suppression and the fewer slices obtained per acquisition. Chemical shift imaging is used to differentiate benign from malignant adrenal diseases based on a gradient echo phase cycling technique. Detailed descriptions of MRI findings in adrenal pheochromocytomas, hemorrhage, cysts, adenomas, myelolipomas, and metastases are provided. Most pheochromocytomas appear markedly hyperintense to the liver on T2-weighted images. However, this appearance is not specific as adrenal metastases and adrenal adenomas may occasionally produce a similar appearance. In addition, pheochromocytomas may occasionally be isointense or hypointense to the liver on T2-weighted images. Differentiation of adrenal metastases from adrenal adenomas with MRI is problematic using signal intensity ratios (33% overlap) or T2 calculations. The future of discriminating between adrenal metastases and adenomas may rest with chemical shift MRI, which uses in- and out-of-phase gradient echo pulse sequences for differentiation. This approach relies on the fact that adrenal adenomas contain fat, while adrenal metastases do not. The reported accuracy of chemical shift imaging in differentiating between adrenal adenomas and adrenal metastases ranges from 96 to 100%. An algorithmic approach to differentiating benign from malignant adrenal diseases is presented that relies on an initial noncontrast CT with CT attenuation values obtained from the adrenal mass. If CT attenuation values are less than zero, the mass is characterized as benign. If the mass remains indeterminate after CT, chemical shift MR is performed. If the mass remains indeterminate after MR, biopsy is required.

Adenoma↗

Results of laparoscopic adrenalectomy for suspected and unsuspected malignant adrenal neoplasms.

BACKGROUND: Laparoscopic resection for malignant adrenal tumors is controversial, because they are rare and limited data exist in the literature. HYPOTHESIS: Laparoscopic adrenalectomy for malignant adrenal tumors is safe and effective. PATIENTS AND METHODS: Twenty-three patients who had a laparoscopic approach for suspected and unsuspected malignant adrenal tumors were studied retrospectively. The adrenal mass was suspected to be metastatic if the patient had a history of previous extra-adrenal primary malignancy and/or positive fine-needle aspiration cytologic findings. A primary adrenal cancer was suspected if there were positive fine-needle aspiration cytologic findings and/or a malignant adrenal imaging phenotype. MAIN OUTCOME MEASURES: (1) Margins of tumor resection, (2) tumor recurrence (locoregional, port site, and distant), and (3) disease-free survival. RESULTS: Twenty-three patients (15 men and 8 women) had 24 laparoscopic procedures (20 adrenalectomies, 3 biopsies, and 1 diagnostic laparoscopy). Permanent histologic specimens in the 23 patients showed 5 adrenocortical cancers, 1 undifferentiated adrenal cancer, 13 adrenal metastases, 2 lymphomas, and 2 cases with no evidence of tumor. Clinically suspected adrenal metastases were true positive in 19 patients (83%). The sensitivity of fine-needle aspiration cytology was 57% (n = 7). Only 1 of 6 patients with primary adrenal cancer was suspected to have a malignant tumor preoperatively. The tumor resection margin was negative in all adrenalectomies. There were 3 locoregional recurrences (2 local and 1 lymph node metastasis) in the 6 patients with primary adrenal cancer, no port site recurrences, and 4 distant recurrences in 13 patients with metastatic adrenal tumors. The disease-free survival was 65% at a mean follow-up time of 3.3 years (range, 1-7 years). CONCLUSIONS: A laparoscopic approach in patients with suspected adrenal metastasis can be both diagnostic and therapeutic, and achieves complete tumor resection. In contrast, laparoscopic adrenalectomy for clinically unsuspected adrenocortical cancer is associated with a high recurrence rate. Furthermore, preoperative fine-needle aspiration cytology for the evaluation of suspected malignant adrenal tumors is unreliable.

Adrenal Gland Neoplasms↗

Scintigraphic localization of adrenal lesions in primary aldosteronism.

Dexamethasone suppression adrenal cortical scintiscanning was performed in 87 patients with primary aldosteronism. Fifty patients had adrenal cortical adenomas and 37 had bilateral adrenal hyperplasia. The diagnosis of adrenal cortical adenoma was confirmed by surgery in 49 of 50, and bilateral adrenal hyperplasia was confirmed by adrenal vein aldosterone sampling in 33 and at operation in four. Dexamethasone suppression adrenal scintigraphy correctly identified the lesion(s) in 82 of the 87 patients. There were three false-negative and two false-positive adrenal cortical scintiscanning results. Computed tomography was performed in 33 patients and correctly identified 14 of 23 patients with adrenal cortical adenomas and two of 10 patients with bilateral adrenal hyperplasia and bilateral enlarged adrenals, whereas the remaining eight were considered to have normal findings. These data indicate that, when properly performed, adrenal cortical scintigraphy is an accurate and efficacious modality for the localization of adrenal cortical adenomas and in the differentiation of adrenal cortical adenoma from bilateral adrenal hyperplasia in primary aldosteronism.

Adenoma↗

Development, maintenance, and function of the adrenal gland in early postnatal proopiomelanocortin-null mutant mice.

Adult mouse mutants homozygous for an engineered proopiomelanocortin (POMC)-null allele lack macroscopically distinct adrenal glands and circulating adrenal hormones. To understand the basis for this adrenal defect, we compared the development of adrenal primordia in POMC-null mice and littermate controls. POMC-null mutant mice are born with adrenal glands that are morphologically indistinguishable from those of their wild-type littermates. However, in mutants adrenal cells fail to proliferate postnatally and adrenals atrophy until they have disappeared macroscopically in the adult. While present, mutant adrenals are differentiated as evidenced by the presence of enzymes for the final steps in the synthesis of corticosterone, aldosterone, and catecholamines. However, in contrast to adrenals of wild-type littermates, adrenals of POMC-null mutants do not produce corticosterone, not even in response to acute stimulation with exogenous ACTH. They do produce aldosterone; however, it is produced at reduced levels correlating with adrenal size. Transplantation of POMC-null mutant adrenals to adrenalectomized wild-type littermates results in adrenals with normal morphology and production of both corticosterone and aldosterone. These findings demonstrate that POMC peptides are not required for prenatal adrenal development and that POMC peptides in addition to ACTH are required for postnatal proliferation and maintenance of adrenal structures capable of producing both glucocorticoids and mineralocorticoids.

Adrenal Gland Diseases↗

Morphological analysis of adrenal glands: a prospective analysis.

There is a lack of studies to document the weight range of normal adrenal glands. The aims of the current study are to find out the weight range of normal adrenal glands in Chinese patients and to analyze any potential factors affecting it. Adrenal glands not affected by disease were prospectively collected from autopsies on 333 Chinese patients (208 men, 125 women). The weight and longest dimension of each adrenal gland were noted. The impact of various clinicopathological factors on the adrenal weight was studied. In addition, the morphometric features of these adrenal glands were compared with that of 28 surgically resected adrenal glands with cortical adenomas. The mean combined weight of adrenal glands was 11.8 g (range = 5.8 g to 19.9 g). The left adrenal gland was often heavier than the right (mean weight = 6.1 g and 5.7 g respectively) and with a greater longitudinal length than the right (mean length = 5.2 cm and 4.8 cm respectively). Adrenal glands were often heavier in male, younger age group (less than 60-yr-old) and patients with history of hypertension or lung cancers. In comparison, the mean weight of right adrenal gland with cortical adenoma was 11.7 g (range = 6 g to 26 g) and that of left adrenal gland with cortical adenoma was 9.4 g (range = 4.6 g to 25 g). This is the first study in the English literature that provides data on the weight of normal adrenal glands in a solely Chinese population. Adrenal weight may be affected by patients' gender, age, laterality of adrenal gland and presence of systemic disease.

Adenoma↗

Ultrasonographic evaluation of the adrenal glands in six dogs with hypoadrenocorticism.

The purpose of this study was to determine the value of ultrasonographic characterization of the adrenal glands in dogs with hypoadrenocorticism. Measurements of adrenal glands were obtained in six dogs with hypoadrenocorticism. The adrenal glands on both sides were shorter (range: left adrenal gland length, 10.0 to 19.7 mm; right adrenal gland length, 9.5 to 18.8 mm) and thinner (range: left adrenal gland thickness, 2.2 to 3.0 mm; right adrenal gland thickness, 2.2 to 3.4 mm) than in normal dogs (range: left adrenal gland length, 13.2 to 26.3 mm; right adrenal gland length, 12.4 to 22.6 mm; left adrenal gland thickness, 3.0 to 5.2 mm; right adrenal gland thickness, 3.1 to 6.0 mm). Statistical analysis revealed a significant reduction in size of the left adrenal gland (p less than 0.05) in dogs with hypoadrenocorticism compared to the left adrenal gland in normal dogs. The results of this study show that atrophy of the adrenal glands in dogs with hypoadrenocorticism seems to lead to an ultrasonographic-measurable reduction in size of the adrenal glands.

Adrenal Glands↗

[Central and peripheral actions of clonidine causing changes of the adrenal medullary functions in spontaneously hypertensive rats].

The central and peripheral effects of clonidine on the adrenal medullary function were investigated in the spontaneously hypertensive rats (SHR). Male 20-25 week old SHR of Wistar Okamoto strain were used (body weight 344.9 +/- 5.7 g). SHR were anesthetized with 50 mg/kg alpha-chloralose and 500 mg/kg urethane intraperitoneally. Tracheae were cannulated and connected to a respirator. Blood pressure and heart rate were recorded via left carotid artery. For the analysis of the adrenal function, adrenal venous catecholamine secretion rates and efferent adrenal nerve discharges were determined. Blood samples were collected from the left adrenal vein of the heparinized animal. Catecholamines in adrenal venous plasma were separated by high performance liquid chromatography and measured spectrofluorometrically using the trihydroxyindole method. Intravenous administration of clonidine decreased adrenal venous catecholamine secretion rates and adrenal nerve activity. Intracerebroventricular administration of clonidine also decreased adrenal nerve discharge rates. Furthermore, after acute splanchnicotomy, clonidine produced a significant decrease in epinephrine secretion rate from the denervated adrenal medulla during electrical stimulation of splanchnic nerve. These findings indicate that the adrenal medulla and the spinal and supraspinal structures are the responsible sites of action of clonidine induced adrenal suppressant effect. The fact that the clonidine induced decrease in adrenal catecholamine secretion rates was approximately parallel to the decrease in preganglionic adrenal nerve discharges in the nerve intact SHR, suggests that the central action of clonidine is important in the adrenal suppressant effect relative to its peripheral action.

Action Potentials↗

Primary aldosteronism: adrenal venous sampling.

BACKGROUND: In primary aldosteronism, high-resolution adrenal computed tomography (CT) increasingly identifies subtle anatomic abnormalities. To interpret the functional significance of adrenal micronodular changes on CT scan, we have reevaluated selective adrenal venous sampling. METHODS: Thirty-four patients with primary aldosteronism were selected prospectively for adrenal venous sampling on the basis of CT findings: normal findings or minimal thickening of an adrenal limb (n = 15), unilateral microadenoma (n = 6), bilateral adrenal nodules (n = 9), or atypical unilateral adrenal macroadenoma (n = 4). RESULTS: Both adrenal veins were catheterized in 33 of 34 patients. Six (40%) of 15 patients with normal or minimal adrenal limb thickening had a unilateral source of aldosterone. Six patients with apparent unilateral microadenoma had ipsilateral aldosterone-producing adenomas. Four (44%) of nine patients with bilateral adrenal masses had a unilateral source of aldosterone secretion. Three of four patients with unilateral atypical adrenal macroadenomas had ipsilateral aldosterone-producing adenomas. CONCLUSIONS: A unilateral source of aldosterone excess may be found in selected patients with adrenal glands that appear normal or show a minimally expanded adrenal limb on CT scan. Findings on adrenal venous sampling are crucial in determining the source of aldosterone excess in patients with bilateral adrenal masses or atypical-appearing macroadenomas.

Adenoma↗

Adrenal angiotensin: origin and site of generation.

BACKGROUND: Circulating angiotensin (Ang) II accumulates in adrenal tissue via binding to Ang II type 1 (AT1) receptors, reaching levels that are 15 to 20 times higher than in blood. Adrenal tissue contains a second renin transcript that gives rise to a truncated prorenin representing a cytosolic form of renin. Here we investigated what percentage of adrenal Ang II originates at adrenal tissue sites, and whether intracellular renin contributes to adrenal angiotensin production. METHODS: Concentrations of endogenous and iodine-125 (125I)-labeled Ang I and II were measured in adrenal tissue and blood from pigs after 125I-Ang I infusion. RESULTS: In the adrenal tissue in all animals, 125I-Ang I was undetectable. In untreated pigs, adrenal 125I-Ang II was 17 +/- 1 times arterial 125I-Ang II, and tissue Ang I and II were 5 +/- 1 and 388 +/- 40 times higher than plasma Ang I and II. The AT1 receptor antagonist eprosartan reduced adrenal 125I-Ang II accumulation by 80%, and increased plasma Ang II to a greater degree than tissue Ang II. As a consequence, eprosartan equally reduced the tissue/plasma concentration ratios of both Ang II and 125I-Ang II. Captopril did not alter 125I-Ang II accumulation, and acutely, but not chronically, reduced the adrenal Ang II/I ratio. CONCLUSIONS: More than 90% of adrenal Ang II originates at adrenal tissue sites. Local adrenal Ang II generation occurs extracellularly and is followed by internalization via AT1 receptor-mediated endocytosis. Enhanced angiotensin generation, combined with incomplete AT1 receptor blockade and the large adrenal AT1 receptor reserve, explains why eprosartan increased rather than decreased adrenal Ang II. Our data do not support angiotensin generation by truncated prorenin.

Acrylates↗

Effect of cholinergic blockade on glucocorticoid regulation of NPY and catecholamines in the rat adrenal gland.

Catecholamines and neuropeptide Y (NPY) levels were determined in the adrenals of rats treated for 2.5 days with chlorisondamine (6 mg/day), a nicotinic ganglionic blocking agent, metyrapone (66 mg/day), an inhibitor of the 11 beta-hydroxylase activity or both metyrapone and chlorisondamine. Chlorisondamine induced a significant increase in adrenal weight (31%) without significant rise in hypothalamic CRH content, plasma ACTH level and plasma corticosterone concentration. This drug was unable to affect significantly dopamine (DA), norepinephrine (NE) and epinephrine (E) content of the adrenals; in contrast, it induced a significant decrease (90%) of plasma NE and E levels. Chlorisondamine induced no change in adrenal NPY content as well as NPY mRNA level determined by Northern blot but significantly increased NPY plasma level. Metyrapone-treatment induced a significant drop of plasma corticosterone level and elicited a significant reduction of hypothalamic CRH content, a rise (460%) of the plasma ACTH concentration associated with a significant increase (18%) of the adrenal weight. A marked increase of DA (240%) and significant decrease of E (22%) in the adrenal gland were observed in response to metyrapone treatment. In addition, metyrapone induced a drop (23%) in plasma E level. In both the adrenals and the plasma, the ratio E/NE was significantly reduced by metyrapone treatment. Metyrapone elicited a significant increase of adrenal NPY content (88%) as well as of NPY mRNA revealed by Northern blot analysis but was unable to significantly affect NPY plasma level. The effects of chlorisondamine, given in combination with metyrapone on both hypothalamic CRH content and plasma ACTH level, were similar to those induced by metyrapone given alone. Chlorisondamine-mediated pharmacological ganglionic blockade increased metyrapone-induced adrenal hypertrophy and adrenal DA storage but prevented metyrapone-induced depletion of adrenal E as well as increase of the adrenal NPY mRNA level and NPY content. Chlorisondamine-induced elevation of plasma NPY level was not observed under metyrapone treatment. Present data suggest that the increase in adrenal NPY synthesis in response to metyrapone treatment is mediated by transsynaptic cholinergic activation and implies nicotinic receptors. On the other hand, adrenal TH may be regulated by additional or different mechanisms, which possibly involve nonnicotinic transmission. Present work also suggests that the suppression of the glucocorticoid feedback inhibition of hypothalamic CRH neurons could stimulate sympathoneuronal outflow and consequently elicit transsynaptic cholinergic activation of adrenal neuropeptide Y gene expression.

Adrenal Glands↗

Decreased expression of cytochrome P450 17 alpha-hydroxylase mRNA in senescent bovine adrenal gland.

To investigate the mechanisms of age-related decline in synthesis of adrenal androgen, we studied the contents of cortisol (F) and dehydroepiandrosterone (DHEA) and the amounts of cytochrome P450 17 alpha-hydroxylase (P450c17) mRNA and cytochrome P450 11 beta-hydroxylase (P450c11) mRNA in young (1 year old) and senescent (10-12 years old) bovine adrenal glands. We also examined effects of ACTH (10(-7) M) on the secretion of F and DHEA and on the induction of P450c17 and P450c11 mRNA expression in cultured adrenal cells from young and aged cows. The content of DHEA in adrenal glands and the secretion of DHEA in response to ACTH in cultured adrenal cells from senescent cow were lower than those from young cow, while the content and ACTH-stimulated secretion of F in senescent adrenals were of a similar level to those in young adrenals. The adrenal gland from aged cow showed a significantly lower level of P450c17 mRNA compared with young bovine adrenal. However, P450c11 mRNA was expressed in senescent adrenal glands at the same level as that in young adrenals. The induction of P450c17 mRNA by ACTH (10(-7) M for 24 h) in cultured adrenal cells from aged cow also showed a decline compared with that from young cow, although there was no difference the ACTH-induced accumulation of P450c11 mRNA in cultured adrenal cells between young and senescent cow. These results suggested that the expression of P450c17 mRNA decreased in aged bovine adrenal, which may cause the age-associated decline in biosynthesis of adrenal androgen.

Adrenal Glands↗